EC approval is based on results from the replicate Phase III INPULSIS® trials, involving 1,066 patients from 24 countries

Professor Klaus
Dugi, Chief Medical
Officer, Boehringer
Ingelheim

Ingelheim, Germany, 19 January 2015 – Boehringer Ingelheim today announced that the European Commission (EC) has approved nintedanib* for the treatment of idiopathic pulmonary fibrosis (IPF), following an expedited review and positive CHMP opinion on 20 November 2014. Nintedanib* will be marketed in the EU under the brand name OFEV®. IPF is a debilitating and fatal lung disease – with a median survival of 2-3 years after diagnosis.

“Approval of this treatment for patients in the EU is a significant step towards meeting the substantial unmet need in IPF. Patients suffering from this chronic, debilitating disease can now be offered a new treatment option that has been shown to have a clinically meaningful effect on their disease,” said Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim. “This approval is another milestone in Boehringer Ingelheim’s ongoing efforts with regard to innovation in rare diseases in general and our continuing research for the benefit of patients affected by such a dreadful disease as IPF in particular.”

EC approval is based on results from the replicate Phase III INPULSIS® trials, involving 1,066 patients from 24 countries. INPULSIS® results showed that nintedanib* slowed disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types including patients with early disease (forced vital capacity (FVC) >90% pred), limited radiographic fibrosis (no honeycombing) on high resolution computed tomography (HRCT) and those with emphysema.2 Nintedanib*, only one capsule twice a day, is the first targeted treatment for IPF to consistently meet the primary endpoint in two identically designed Phase III trials. Nintedanib* has been shown to significantly reduce the risk of adjudicated acute exacerbations‡ by 68%.2

Professor Luca
Richeldi, Professor of
Respiratory Medicine,
Chair of Interstitial
Lung Disease at the
University of
Southampton, United
Kingdom

Study investigator Professor Luca Richeldi, Professor of Respiratory Medicine, Chair of Interstitial Lung Disease at the University of Southampton, United Kingdom, said “Until recently, treatment options for patients with IPF were limited. The approval of nintedanib* in the EU gives patients with a life threatening illness a choice of therapy with proven efficacy. Clinical data demonstrate that nintedanib* reduces the annual decline of lung function by approximately half. Data also showed that nintedanib* reduced the risk of acute exacerbations, which can lead to hospitalisation and death.”

Worldwide IPF affects as many as 14–43 people per 100,000.3,4 It most commonly affects people over the age of 50.5 IPF causes permanent scarring of the lungs and decreases the amount of oxygen the lungs can supply to major organs of the body.6,7

“It’s great that there is now a choice of treatments for IPF patients. This approval provides important hope for patients and caregivers living with this awful disease,” said Dr Toby Maher, Consultant Respiratory Physician at the Royal Brompton Hospital in London, United Kingdom.

Notes to Editor

About the INPULSIS® Phase III trials with nintedanib*​
The double blind, randomised, placebo-controlled trials involving 1,066 patients across 24 countries evaluated the effect of oral nintedanib* 150 mg twice daily on the annual rate of decline in forced vital capacity (FVC) in patients with IPF over 52 weeks. The trials had an identical design, matched dosing, inclusion criteria and endpoints.2,8 The primary endpoint was the annual rate of decline in FVC (expressed in mL over 52 weeks). Key secondary endpoints were: change from baseline in health-related quality of life, as assessed by the Saint George’s Respiratory Questionnaire (SGRQ) and time to first acute exacerbation.

Nintedanib* significantly reduced the risk of adjudicated acute exacerbations‡ by 68% in the pooled data set

Nintedanib* significantly reduced the risk of adjudicated acute exacerbations‡ by 68% in the pooled data set

In both INPULSIS® trials, the most common adverse events were gastrointestinal in nature, of mild or moderate intensity, generally manageable and rarely leading to treatment discontinuation.2 The proportion of patients with serious adverse events was similar in all groups.2 The most frequent adverse event in the nintedanib* groups was diarrhoea, reported in 62% vs. 19% (INPULSIS®-1) and 63% vs. 18% (INPULSIS®-2) of patients in the nintedanib* vs. placebo groups, respectively. Less than 5% of patients in the nintedanib* groups of INPULSIS®-1 and INPULSIS®-2 discontinued treatment due to this event.2

About OFEV® (nintedanib*)
Nintedanib* is a small molecule tyrosine kinase inhibitor developed by Boehringer Ingelheim for IPF.9 Nintedanib*, one capsule twice a day, slows disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types.2 This included patients with early disease (FVC >90% pred), limited radiographic fibrosis (no honeycombing) on high resolution computed tomography (HRCT) and those with emphysema.2 Only nintedanib* reduces adjudicated acute exacerbations‡ by 68%.2 This can be crucial given that approximately 50% of patients hospitalised for an acute IPF exacerbation die during hospitalisation.10 Side effects with nintedanib* can be effectively managed in most patients.2

Nintedanib* targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs. Most importantly nintedanib* inhibits platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).9,11,12 It is believed that nintedanib* reduces disease progression in IPF and slows the decline in lung function by blocking the signaling pathways that are involved in fibrotic processes.9,11,13​

The FDA approved OFEV® (nintedanib*) for the treatment of IPF on 15 October 2014

The Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for nintedanib* for the treatment of IPF on 20 November 2014

On 21 November 2014, the European Commission granted EU marketing authorisation for Vargatef® (nintedanib*) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology, after first-line chemotherapy

About idiopathic pulmonary fibrosis
IPF is a chronic, progressive, severely debilitating and ultimately lethal lung disease for which there are limited treatment options.1 IPF affects as many as 14–43 people per 100,000 worldwide.3,4 IPF is characterised by progressive scarring of lung tissue and loss of lung function over time.7,11 Development of scarred tissue is called fibrosis.1 Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream and vital organs do not get enough oxygen.6 As a result, individuals with IPF experience shortness of breath, a non-productive cough and often have difficulty participating in everyday physical activities.14​

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

Footnotes

*Nintedanib is approved under the brand name OFEV® in the US and EU for use in patients with IPF. Nintedanib is under regulatory review by health authorities in other countries

**INPULSIS® recruited a broad range of patient types – similar to those seen in clinical practice including patients with early disease (FVC > 90% pred), no honeycombing on HRCT and/or concomitant emphysema

‡Adjudicated exacerbations’ was a pre-specified sensitivity analysis in the pooled data set. Time to first investigator-reported exacerbation was a secondary endpoint which was met in TOMORROW and INPULSIS®-2 but not in INPULSIS®-1